2,4-Dichlorophenoxyacetic acid (2,4-D), a broadleaf herbicide with a high incidence of use world-wide, is one chemical in a class study of four peroxisome proliferators being studied by the NTP. NTP has performed toxicokinetic studies of 2,4-D in Sprague-Dawley (S-D) rats, B6C3F1 mice and Syrian hamsters. In contrast to mice and rats, the toxicokinetic behavior in hamsters was complex. One possible explanation for the toxicokinetic behavior is extensive enterohepatic circulation. To investigate this possibility, biliary elimination of 2,4-D following oral administration was investigated in all three species. Techniques for cannulating mouse bile ducts were developed. Bile flow in cannulated animals was maintained in all three species for up to 6 hours following administration of 14C 2,4-D. Total recovery was greatest in male mice. Female mice and rats of both sexes were intermediate. Hamsters eliminated least of the administered dose in bile, virtually eliminating the possibility that the complex toxicokinetic behavior seen in this species was due to enterohepatic recirculation. Phenolphthalein, present in many laxative preparations was the subject of a recent NTP 2-year study. Evidence for increased tumor incidence in multiple organs was found in both sexes and both species. As part of the effort to provide more information about how the NTP study may apply to human risk, metabolism and disposition studies with 14C phenolphthalein in male and female F344 rats and B6C3F1 mice were initiated. These studies were performed with single oral doses equivalent to a human therapeutic dose and doses that fell within the range of doses found to be carcinogenic in the 2-year study. There was no significant retention or accumulation of radioactivity in tissues by 72 hr. Covalent binding, as measured by non-extractable radioactivity, was at or below the pmol/mg of protein range in liver, bone marrow and ovary, target organs in the NTP study.